BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

The Chinese Neonatal Network(CHNN) was established in 2018 with the mission of establishing a national collaboration platform, conducting high-quality and collaborative research, and ultimately improving the quality of neonatal-perinatal care and health in China.At present, 112 hospitals across the country have joined CHNN.CHNN has established a national standardized cohort of very premature infants/very low birth weight infants with >10 000 enrollments each year, has been leading data-driven collaborative quality improvement initiatives, conducting multicenter clinical studies, and performing multi-level training programs.Guided by the principles of collaboration and sharing, data-driven, continuous improvement, and international integration, CHNN has become an important platform for clinical and research collaboration in neonatal medicine in China.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective:To evaluate the value of plasma aldosterone concentration (PAC)/renin concentration (PRC) ratio (ARR) combined with aldosterone, renin, and sodium/potassium ratio in the diagnosis of primary aldosteronism (PA).Methods:From January 2017 to October 2019, 105 patients were admitted to our hospital and diagnosed as PA and essential hypertension (EH) by clinical manifestations, laboratory examination and surgical pathological biopsy.The optimum cut-off point of ARR, PRC, PAC, plasma sodium-potassium ratio were determined by the Receiver Operating Characteristic (ROC). The sensitivity, specificity and Youden index at the optimum cut-off point were calculated in a separate test. By means of diagnostic test, the best cut-off points of ARR were tested in series with the best cut-off points of PRC, PAC and serum sodium/potassium ratio, respectively, and their specificity were calculated.Results:The area under the AUC of supine ARR was greater than that of vertical ARR (0.966 vs 0.946, Z= 1.380, P= 0.168), but there was no statistical difference. The optimum cut-off point of supine ARR was 28.64(pg/ml)/(pg/ml), with a sensitivity of 92.4% and specificity of 90.5%. The sensitivity of the combined PRC test was 79.0% and the specificity was 94.3%. The sensitivity of the combined PAC test was 65.7% and the specificity was 95.2%. The sensitivity of the combined serum sodium/potassium ratio was 50.5% and the specificity was 96.2%. The optimal cut-off of vertical ARR was 22.10 (pg/ml)/(pg/ml), with 91.4% specificity and 85.7% specificity. The sensitivity of vertical ARR combined with PRC was 78.1%, specificity was 89.5%. The sensitivity of combined PAC was 74.3%, specificity was 92.4%, and the sensitivity of combined sodium/potassium ratio was 50.5%, specificity was 95.2%. Conclusions:There was little difference in the diagnostic performance of PA between vertical and supine ARR values. The specificity of PA screening by ARR alone was high, and the specificity and accuracy of PA diagnosis could be improved by combining PRC, PAC and sodium/potassium ratio.

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

Objective? To explore effects of CoughAssist on sputum excretion efficacy among patients with intensive care unit-acquired weakness (ICU-AW). Methods? From January 2016 to December 2017, we selected 84 ICU-AW patients with mechanical ventilation of ICU in Hu'nan Provincial People's Hospital by convenience sampling. All of the patients were divided into control group and observation group with the random number table, 42 cases in each group. Two groups all received routine treatment and nursing. On this basis, observation group carried out CoughAssist therapy. We compared the sputum excretion effects, results of sputum smear/sputum culture, arterial blood gas indexes, respiratory mechanics indexes, the incidence of ventilator-associated pneumonia (VAP), time of mechanical ventilation, hospital days in ICU and the score of Medical Research Council (MRC) of patients between two groups. Results? There were no statistical difference in the volume of sputum excretion of patients in two groups before dividing groups (P＞0.05). One to three days after treatment, the volume of sputum excretion and number of effective sputum excretion patients in observation group were more than those in control group; the positive rate of sputum culture of patients in observation group was lower than that in control group; the differences were all statistical (P＜ 0.05). The partial pressure of oxygen (PaO2) of observation group was higher than that of control group; the partial pressure of carbon dioxide (PaCO2) of observation group was lower than that of control group; the differences were all statistical (P＜0.05). The pressure support/pressure control (PS/PC) and airway resistance of observation group were lower than those of control group;and the compliance and cough peak flow (PCF) were higher than those of control group with statistical differences (P＜ 0.01). The incidence of VAP, time of mechanical ventilation and hospital days in ICU of observation group were lower than those of control group (P＜0.05). There was no statistical difference in the scores of MRC between two groups (P＞0.05). Conclusions? The application of CoughAssist in ICU-AW patients with mechanical ventilation can improve the sputum excretion effects as well as respiratory function and shorten the time of mechanical ventilation and hospital days in ICU, and improve the clinical effects.

By analyzing the present situation, advantages and challenges of the development of new nurses training in hospitals in the Massive Open Online Course (MOOC) era, it is suggested that the intelligent development of MOOC can not only meet the training needs of new nurses in the new situation, but also promote the application of MOOC in nursing inservice education. It is suggested that we should break the barriers, promote the sharing of high quality resources, improve the construction of curriculum system, strengthen the training supervision and assessment system, increase the policy support, strengthen the cultivation of MOOC technical personnel and technical innovation, and explore the "mixed teaching" model and other initiatives to promote MOOC science and its efficient development.

Objective To isolate bacteriophages against extensively-drug resistant Acinetobacter baumannii from hospital sewage and analyze their biological characteristics.Methods Extensively-drug resistant Acinetobacter baumannii isolated from several hospitals in Shanghai during December, 2013 to July, 2014 were used as host bacteria, adopting double-layer agar method to isolate bacteriophages from raw sewage of these hospitals.The phage with broad host range was selected for further study, including observation of electron microscopic morphology, examination of thermal stability, pH stability and the optimal MOI, drawing of the adsorption, one-step-growth and infection curves, as well as sequencing of the phage genome DNA. Results An extensively-drug resistant Acinetobacter baumannii bacteriophage vB_AbaP_PD-AB9 ( PD-AB9 for short) with broad host range was isolated, and electron microscopy revealed it belonged to Podoviridae family.The optimal MOI of PD-AB9 was 0.001.PD-AB9 remained stable among 4 ℃to 50 ℃and pH 4 to 11.In the adsorption experiment, the adsorption rate of PD-AB9 reached above 95%within 5 min.PD-AB9 had a latent period of 4 min and a burst size of 213.PD-AB9 could obviously restrain the host growth, with faster effect at the higher MOIs (MOI=1, 0.1, 0.01) than at the lower ones (MOI=0.001, 0.000 1).Furthermore, genome of PD-AB9 proved to be a double-stranded linear DNA with size of 40 938 bp and GC content of 39.34%.Conclusions PD-AB9 exhibits good thermal stability, wide pH tolerance range, very fast adsorption, a short latent period, a large burst size and it could quickly cause effective host lysis after infection.Therefore, PD-AB9 is promised to act as a new antimicrobial agent to control drug-resistant Acinetobacter baumannii infections and its bio information remains to be further studied.

Objective:To observe the changes of blood glucose,insulin and dipeptidyl peptidase-Ⅳ(DPP-Ⅳ/CD26)on type 2 diabetes mellitus in rabbits after HUCBSC( human umbilical cord blood stem cells) transplantation. Methods:18 rabbits were randomly divided into normal control group (6 rats,Group C) and diabetic model group (12 rats). After preparation model of type 2 diabetes,and 6 rats of them were treated with HUCBSC ( CD45+,CD34-) transplantation by ear vein transfusion ( Group A) ,and 6 rats were treated with PBS(Group B). All three groups of rabbits were fed for 4 weeks,and the blood glucose was monitored every day,and the level of blood insulin and DPP-IV/CD26 were measured every week. Results:The negative expression rate of CD34 in HUCBSC was 96. 5%. The positive expression rate of CD45 in HUCBSC was 100%. Compared with non transplantation group,the blood glucose and DPP-IV/CD26 in the umbilical cord blood stem cell transplantation group were gradually decreased,and insulin level was gradually increased, the difference was statistically significant (P<0. 01). Conclusion:HUCBSC were round or oval,with adherent growth,HUCBSC trans-plantation can significantly reduce blood glucose, increase insulin secretion, reduce the level of DPP-IV/CD26, the immunological phenotype of HUCBSC was CD45+,CD34-,thus providing a new theoretical basis for the clinical treatment of diabetes and its complica-tions.